Behavioral and Brain Sciences

Short Communication

Peripheral and central hyperexcitability: Differential signs and symptoms in persistent pain

Terence J. Coderre a1 and Joel Katz a2
a1 Pain Mechanisms Laboratory, Clinical Research Institute of Montreal; Centre de recherches en sciences neurologiques et département de médecine, Université de Montréal; Department of Psychology, McGill University, Montreal, Quebec, Canada, H2W IR7
a2 Department of Psychology and Acute Pain Research Unit, The Toronto Hospital; Departments of Behavioral Science and Anaesthesia, University of Toronto, Toronto, Ontario, Canada M5S 2C4


This target article examines the clinical and experimental evidence for a role of peripheral and central hyperexcitability in persistent pain in four key areas: cutaneous hyperalgesia, referred pain, neuropathic pain, and postoperative pain. Each suggests that persistent pain depends not only on central sensitization, but also on inputs from damaged peripheral tissue. It is instructive to think of central sensitization as comprised of both an initial central sensitization and an ongoing central sensitization driven by inputs from peripheral sources. Each of these factors, initial sensitization, ongoing central sensitization, and inputs from peripheral sources, contributes to the net activity in dorsal horn neurons and thus influences the expression of persistent pain or hyperalgesia. Since each factor, peripheral inputs and central sensitization (initial or ongoing), can contribute to both the initiation and maintenance of persistent pain, therapies should target both peripheral and central sources of pathology.

Key Words: hyperalgesia; neurogenic inflammation; neuropathic pain; nociception; phantom limb pain; plasticity; postoperative pain; pre-emptive analgesia; referred pain; sensitization.